1. Field of the Invention (Technical Field)
The present invention provides linear and cyclic peptidomimetics that are specific for one or more melanocortin receptors, and which may be used in the treatment of a wide variety of diseases, syndromes and conditions.
2. Background Art
Melanocortin Receptors. A family of melanocortin receptor types and subtypes have been identified, including melanocortin-1 receptors (MC1-R) expressed on normal human melanocytes and melanoma cells, melanocortin-2 receptors (MC2-R) for ACTH (adrenocorticotropin) expressed in cells of the adrenal gland, melanocortin-3 and melanocortin-4 receptors (MC3-R and MC4-R) expressed primarily in cells in the hypothalamus, mid-brain and brainstem, and melanocortin-5 receptors (MC5-R), expressed in a wide distribution of central nervous system and peripheral tissues.
A wide variety of diseases, conditions and syndromes have been identified for which compounds specific for one or more melanocortin receptors may have utility. For example, compounds that are specific for MC1-R, particularly agonists, may be useful as tanning agents by increasing melanin production. Compounds specific for MCR-1 and MCR-3 may be useful in regulation of inflammatory processes. Compounds specific for MC3-R or MC4-R are believed to be useful in regulation of energy homeostasis, including use as agents for attenuating food intake and body weight gain, for use in treatment of anorexia, as a weight gain aid, for treatment of obesity, and treatment of other food intake and metabolism-related purposes. Compounds specific for MC3-R and MC4-R can further be used as agents for treatment of sexual dysfunction, including male erectile dysfunction and female sexual dysfunction. Compounds specific for MC4-R can further be used as agents for treatment of alcohol abuse, anxiety and related conditions.
Both peptide and small molecule melanocortin receptor-specific compounds have been developed and explored for treatment of certain of the foregoing and other conditions. However, to date no melanocortin receptor-specific compound has been approved for any clinical indication, and very few have been tested in human clinical trials.
In general, melanocortin receptor-specific peptides have limitations associated with peptide-based drugs. These include enzymatic degradation, short circulation half life, limited bioavailability, inadequate efficacy, short duration of effect, limitations on routes of administration and the like. Thus there remains a significant need for compounds with the favorable characteristics of peptides, such as high specificity for discrete melanocortin receptors, partial or full agonists, partial or full antagonists, mixed agonist-antagonists, inverse agonists, or antagonists of inverse agonists, but with improved resistance to enzymatic degradation, or improved circulation half life, or improve bioavailability, or improved efficacy, or other advantageous characteristics. It is against this background that the present invention was made.